1. Field of the Invention
This invention relates to a new class of novel organic atropisomeric diphosphine compounds 2,2',6,6'-tetraalkoxy-4,4'-bis(disubstituted-phosphino)-5,5'-disubstituted -3,3'-bipyridine or 2,2',6,6'-tetraalkoxy-4,4'-bis(disubstituted-phosphino)-3,3'-bipyridine compounds {(R)- or (S)-form} and the preparation of these compounds. This invention also relates to the asymmetric catalytic hydrogenation of 2-arylpropenoic acids to give the corresponding 2-arylpropionic acids in high enantiomeric excess. More particularly, the present invention relates to the creation of a class of highly effective chiral catalysts which can be easily recycled through phase-separation from the products. The improved asymmetric catalytic hydrogenation process of the present invention is particularly suitable for use in the synthesis of 2-(6'-methoxy-2'-naphthyl)propionic acid (naproxen) and 2-(p-isobutylphenyl)propionic acid (S)-ibuprofen!.
2. Prior Art
Atropisomeric diphosphines such as BINAP (J. Am. Chem. Soc. 1980, 102, 7932) 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl! and its derivatives have found widespread use in metal-catalyzed asymmetric catalytic reactions. ##STR2##
In particular, BINAP type diphosphines are most useful ligands for enantioselective hydrogenation reactions. Considerable efforts have been undertaken for the design and synthesis of other atropisomeric diphosphine ligands in biphenyl series, for example BIPHEMP (Eur. Pat. No. 104375, 1983); Helv. Chim. Acta. 1988, 71, 897), BICHEP (Chem. Lett. 1989,1849) and MeOBIPHEP (Helv. Chim. Acta. 1991, 74, 370).
The synthesis of BINAP type ligands is difficult. The traditional method requires high temperature (.about.340.degree. C.) and corrosive conditions to convert 2,2'-dihydroxy-1,1'-binaphthene to the key intermediate 2,2'-dibromo-1,1'-binaphthene for the synthesis of BINAP. Scientists at Merck (J. Org. Chem. 1994, 59, 7180) and Takasago (Chiral Tech 1996 ) reported the synthesis of BINAP by using nickel or palladium catalyzed coupling reaction of 2,2'-bis(trifluoromethanesulfonyl)oxy!-1,1'-binaphthyl with diphenylphosphine or diphenylphosphine oxide. This approach requires the expensive trifluoromethanesulfonic anhydride and several extra steps for the synthesis of BINAP, MeOBIPHEP, BIPHEMP and BICHEP. The separation of the homogeneous catalysts from the reaction products is also difficult, making the recycling of the expensive catalysts complicated and consequently the commerical application of these ligands quite expensive.
Naproxen is a nonsteroidal drug with anti-inflammatroy, analgesic and antipyretic activities. It belongs to a group of compounds generally classified as arylpropionic acids or arylalkanoic acids. Many synthetic routes for producing optically pure arypropionic acids have been proposed. These methods include the resolution of a mixture of enantiomers by using a resolving agent such as cinchonidine or glucamine. These resolution procedures require numerous recrystallizations. U.S. Pat. No. 4,542,237 discloses a process for preparing 2-arylpropionic acids and, in particular, a process for preparing naproxen, involving a non-catalytic process which is, therefore, not commerically attractive. The asymmetric hydrogenation of arylpropenoic acid has been previously proposed as a method of producing optically active 2-arylpropionic acids. For example, Campoli et al., U.S. Pat. No. 4,239,914 described catalytic asymmetric hydrogenation of 2-(6-methoxy-2-naphthyl)acrylic acid utilizing a rhodium catalyst containing a chiral bidentate phosphine ligand, e.g. DIPAMP, DIOP or PNNP but the enantiomeric excess of the desired product was reported to be only around 70% or less.
Noyori et al., reported the asymmetric hydrogenation of 2-(6'-methoxy-2'-naphthyl)propenoic acid with a catalytic amount of Ru(S)-BINAP!(OAc).sub.2 at about 13800 KPa H.sub.2 to give naproxen in J. Org. Chem. 1987, 52,3174-3176.
Chan et al., also reported the asymmetric catalytic hydrogenation of 2-arylpropenic acids with Ru-BINAP type catalysts to produce naproxen in U.S. Pat. No. 4,994,607 and U.S. Pat. No. 5,144,050.
For the economical production of naproxen, S-ibuprofen and other similar products, it is highly desirable to invent a new class of catalysts which are more effective than Ru(BINAP) and are easily separated from the reaction products.